We are studying the pathobiology of the arterial wall, particularly in relation to the response after endothelial injury, in terms of endothelial proliferation and regeneration, myointimal proliferation, and the regulation of these processes. We have found that heparin (anticoagulant and non-anticoagulant), both in vivo and in vitro, inhibits vascular smooth muscle cell proliferation. We are characterizing the effects of modified heparins and heparin fragments in terms of inhibitory and anticoagulant effects. Furthermore, growth-arrested endothelial cells secrete a heparin-like inhibitor of smooth muscle cell proliferation. We are characterizing the nature of this inhibitor and the mechanism of its effect.